The focus of our work is the regulation of the G1/S transition in the budding yeast, S. cerevisiae. Previous work in several labs, including ours, has established the CLN1, CLN2, and CLN3 genes of yeast as critical in regulation of this transition, both by external factors (hormones, nutrients) and internal factors (cell size). The homology of these genes with cyclins, and their genetic and biochemical interactions with the product of the cdc2 homolog in this organism, CDC28, combined with the apparent specificity of their action to the G1/S transition (as opposed to the G2/M transition for previously described cyclins) suggests the idea that the CLN proteins may be 'G1 cyclins'. Since the G1/S transition is a primary point of regulation in many organisms, including humans, and since the regulation of this transition is grossly abnormal in cancer, it is important to determine the mechanism of action and regulation of CLN genes, as well as to determine the universality through evolution of the system. These are the issues addressed in this application.